It may be possible to use the placenta to devise a test that will predict which infant born to an HIV-infected mother will acquire HIV infection. Based upon our preliminary observations in 30 placentas of HIV-infected women, we believe that we can detect HIV in the placental villi, generally in the fetal trophoblastic layer, and that this finding appears to correlate with clinical outcome in the infant. Based upon in situ hybridization technology and confocal imaging microscopy we have detected HIV-RNA in fetal trophoblastic cells in almost all of those infants that subsequently were shown to have HIV infection by HIV culture and/or PCR technology, p24 Ag determination, and clinical symptoms. These findings pertain to 9 of the maternal/infant pairs of the 30 patients studied; longer follow-up is necessary to determine the correlation of clinical outcome of the remaining children. Because of these preliminary results, we plan to attempt prenatal diagnosis of HIV infection by performing in situ hybridization and confocal imaging studies on tissue obtained by chorionic villus sampling. Our specific aims are: 1) to enroll 30 HIV-infected and 5 control pregnant women per year for 4 years into this study of HIV infection in the fetal placenta; to obtain 30 placentas and examine for HIV-RNA using in situ hybridization technology and confocal imaging microscopy, 2) to enroll 10 HIV-infected and 5 control (genetic prenatal. diagnosis) pregnant women (a subset of the 30) each year for determination of HIV transcription in the chorionic villus, 3) to correlate the clinical outcome and HIV-infection status in the infants born to the subjects studied in Specific Aims 1 and 2 with the results of detection of HIV-RNA, HIV-antigens, cell surface markers, viral cofactors, and morphology in the chorionic villi (biopsy specimen and tissue culture cells) and placentas, and 4) to determine the factors important in permitting HIV infection of chorionic villus samples in vitro. It is possible that the results of this research project will have immediate and significant impact upon our ability to make an early, possibly prenatal, diagnosis of HIV infection in infants born to HIV-infected women.